tbuckley/cabot-search huggingface dataset:
A phase Ia/Ib study of CBP-1008, a bispecific ligand drug conjugate, in patients with advanced solid tumors.
Authors: Lingying Wu, Lin Shen, Xichun Hu, Ning Li, Dan Liu, Jian Zhang, Robert Huang, Yan Teng, Li Li, Bin Zhang, Youzhong Zhang, Yi Huang, Ying Wang, Junyan Wu, Yulong Zheng, SuXia Luo, Yi Ba, Zhongsheng Tong, Xian Wang, Ge Lou
Journal: Journal of Clinical Oncology (2022)

3000 Background: Folate receptor α (FRα) and vanilloid subfamily member 6 of transient receptor potential channels (TRPV6) are overexpressed in many solid tumors hence could be promising therapeutic targets. CBP-1008 is a first-in-class bi-specific ligand drug targeting FRα and TRPV6 carrying monomethyl auristatin E (MMAE) as payload. Here we report the first-in-human, multicenter, phase Ia/Ib study designed to explore the safety, pharmacokinetics and efficacy of CBP-1008 in advanced solid tumors. Methods: CBP-1008 was administered by intravenous infusion. Phase Ia study included a dose-escalation period initiated by accelerated titration (0.015, 0.03mg/kg d1,15; q28d) and then switched to 3+3 scheme (0.12, 0.15, 0.17, 0.18mg/kg d1,15; q28d) and a dose expansion period. Phase Ib clinical expansion study included 3 cohorts, platinum-resistant ovarian cancer (OC), metastatic triple negative breast cancer (TNBC) and other solid tumors. The primary objective was to assess the safety and preliminary efficacy. Results: As of January 13, 2022, 106 patients received at least one dose of study drug were enrolled (phase Ia: n = 30; phase Ib: n = 76) and received median 3 prior regimens. Included tumor species were OC (n = 52), TNBC (n = 20), ER+/Her2+ breast cancer (BC) (n = 16), lung cancer (n = 3), pancreatic cancer (n = 2) and others (n = 13). In phase Ia study, DLTs were observed in 3 patients (0.12, 0.15, 0.18mg/kg, n = 1 each), including grade 4 hypophosphatemia, neutropenia, febrile neutropenia, and grade 3 hyperglycemia, alanine aminotransferase (ALT). MTD was not yet reached. Majority of adverse events were mild to moderate. The most common grade 3/4 treatment-emerging adverse events (TEAEs) were neutropenia (37.7%), AST elevation (6.6%), ALT elevation (5.7%), hyperglycemia (2.8%), hypohemoglobinemia (2.8%) and nausea (1.9%). Drug-related death was not observed. A total of 69 patients at dose of 0.15mg/kg or above were evaluable for efficacy assessment. There were 11 patients achieved partial response (PR) (OC n = 8, ER+/Her2+ BC n = 2, TNBC n = 1) and 30 patients achieved stable disease (SD). In 32 advanced platinum-resistant OC patients with FRα and/or TRPV6-positive expression, 6 PR and 16 SD were observed. Moreover, 6/18 PR (33.3%) and 8/18 SD (44.4%) were observed in enriched OC patients who showed high score of FRα/TRPV6 receptor. Conclusions: The preliminary results showed that CBP-1008 has manageable safety profile. Antitumor activity was observed in patients with FRα/TRPV6 receptor expression, especially in platinum-resistant OC cohort with high score of the two receptors. Clinical trial information: NCT04740398.
Factors associated with short- and long-term survival in metastatic HER2+ breast cancer.
Authors: Jose Pablo Leone, Julieta Leone, Carlos Teodoro Vallejo, Heather Anne Parsons, Michael J. Hassett, Nancy U. Lin
Journal: Journal of Clinical Oncology (2022)

1047 Background: There have been significant therapeutic advances for HER2+ metastatic breast cancer (MBC) over the past decade. The aim of this study was to evaluate prognostic factors in metastatic HER2+ disease and their relationship with short- and long-term overall survival (OS) in the modern era. Methods: We evaluated patients (pts) with de novo metastatic HER2+ breast cancer diagnosed between years (y) 2010 and 2018, reported in SEER. Univariate analyses were performed to determine the effect of each variable on OS. Significant variables were included in a multivariate Cox model for OS that evaluated all pts diagnosed 2010 – 2018. Univariate and multivariate logistic regression was used to evaluate the association of each variable with short (&lt; 2 y) and long (≥ 5 y) term OS. To allow sufficient follow up, only pts diagnosed 2010 – 2016 were included in the logistic regression for OS &lt; 2 y, and only those diagnosed 2010 – 2014 were included for OS ≥ 5 y. Results: We included 5,576 pts with a median follow up of 48 months (IQR 25 – 73 months). Median OS was 41 months. The proportion alive at 2 y, 5 y, and 8 y, was 63.3% (95% CI 62.0% - 64.7%), 37.8% (95% CI 36.2% - 39.4%) and 26.8% (95% CI 24.8% - 28.9%), respectively. In multivariate analysis for OS, older vs younger age (HR 2.5), black vs white pts (HR 1.4), non-ductal non-lobular vs ductal (HR 2.7), bone metastases vs not (HR 1.2), brain metastases vs not (HR 1.8), liver metastases vs not (HR 1.6), lung metastases vs not (HR 1.3), 6 metastatic organ sites vs 1 (HR 3.6), ER/PR- vs + (HR 1.3), &lt; $35k income vs ≥ $75k (HR 1.8), and being diagnosed in earlier years (HR 1.06 per each prior year) had significantly worse OS (all p≤0.044). Similar results were seen for breast cancer-specific survival. Factors associated with &lt; 2 y OS in adjusted models were older age (OR 3.8), black race (OR 1.5), non-ductal non-lobular (OR 4.6), brain metastases (OR 3.0), liver metastases (OR 2.0), lung metastases (OR 1.6), ER/PR- (OR 1.7) and lower income (OR 1.6), all p &lt; 0.04. Number of metastatic organ sites was not significant in this model. Factors associated with ≥ 5 y OS in adjusted models were younger age (OR 2.9), white vs black race (OR 1.7), fewer metastatic organ sites (OR 2.6), ER/PR+ (OR 1.3), and higher income (OR 3.3), all p &lt; 0.02. Specific organ sites (bone, brain, liver and lung) were not significant in this model. Conclusions: In this cohort of pts with de novo HER2+ MBC, OS improved significantly over the study period, and a considerable proportion of pts were still alive at 8 y. Factors associated with shorter survival included older age, black race, lower income, and the presence of visceral or brain metastases. Long-term (≥ 5 y) survival was associated with both demographic (younger age, white race, higher income) and tumor-related (fewer metastatic sites, ER/PR positivity) factors.
Long COVID-19 in patients with cancer: Report from the National COVID Cohort Collaborative (N3C).
Authors: Noha Sharafeldin, Vithal Madhira, Qianqian Song, Benjamin Bates, Amit Kumar Mitra, Feifan Liu, Timothy Bergquist, Jing Su, Fang-Chi Hsu, Umit Topaloglu
Journal: Journal of Clinical Oncology (2022)

1540 Background: Post-acute sequelae of SARS-CoV-2 or long COVID, is characterized by persistence of symptoms and/or emergence of new symptoms post COVID-19 infection. As evidence accumulates and national initiatives arise to address this increasingly prevalent syndrome, characterization of specific patient groups is still lacking including patients with cancer. Using a nationally representative sample of over 4.3M COVID-19 patients from the National COVID Cohort Collaborative (N3C), we aim to describe characteristics of patients with cancer and long COVID. Methods: We employed two approaches to identify long COVID patients within N3C: i) patients presenting to a long COVID clinic at four N3C sites and ii) patients diagnosed using the recently introduced ICD-10 code: U09.9 Post COVID-19 condition, unspecified. We included patients with at least one positive COVID-19 diagnosis between 1/1/2020 and 2/3/2022. Patients had to survive at least 90 days from the date of their COVID-19 diagnosis. Analyses were performed in the N3C Data Enclave on the Palantir platform. Results: A total of 1700 adult patients with long COVID were identified from the N3C cohort; 634 (37.3%) were cancer patients and 1066 were non-cancer controls. The most common represented cancers were skin (21.9%), breast (17.7%), prostate (8.3%), lymphoma (8.0%) and leukemia (5.7%). Median age of long-COVID cancer patients was 64 years (Interquartile Range: 54-72), 48.6% were 65 years or older, 60.4% females, 76.8% non-Hispanic White, 12.3% were Black, and 3% Hispanic. A total of 41.1% were current or former smokers, 27.7% had an adjusted Charlson Comorbidity Index score of 0, 18.6% score of 1 and 11.2% score of 2. A total of 57.2% were hospitalized for their initial COVID-19 infection, the average length of stay in the hospital was 9.6 days (SD: 16.7 days), 9.1% required invasive ventilation, and 13% had acute kidney injury during hospitalization. The most common diagnosis among the non-cancer long COVID patients was asthma (26%), diabetes (17%), chronic kidney disease (12%), heart failure (9.4%), and chronic obstructive pulmonary disease (7.8%). Among long COVID patients, compared to non-cancer controls, cancer patients were more likely to be older (OR = 2.4, 95%CI: 1.1-5.4, p = 0.03), have comorbidities (OR = 4.3, 95%CI: 2.9-6.2, p &lt; 0.0001), and to be hospitalized for COVID-19 (OR = 1.3, 95%CI: 1.0-1.7, p = 0.05), adjusting for sex, race/ethnicity, body mass index and smoking history. Conclusions: In a nationally representative sample of long COVID patients, there was a relative overrepresentation of patients with cancer. Compared to non-cancer controls, cancer patients were older, more likely to have more comorbidities and to be hospitalized for COVID-19 warranting further investigation to identify risk factors for long COVID in patients with cancer.
A phase 1/2 study of BLU-945 in patients with common activating <i>EGFR</i>-mutant non–small cell lung cancer (NSCLC): SYMPHONY trial in progress.
Authors: Elaine Shum, Yasir Y Elamin, Zofia Piotrowska, David R Spigel, Karen L. Reckamp, Julia K Rotow, Daniel Shao-Weng Tan, Sun Min Lim, Tae Min Kim, Chia-Chi Lin, Terufumi Kato, Jagan Parepally, Faris Albayya, Melinda Louie-Gao, Tessa Weinig, Alena Zalutskaya, Koichi Goto
Journal: Journal of Clinical Oncology (2022)

TPS9156 Background: Although EGFR-targeted therapies have improved outcomes in patients with EGFR-mutant ( EGFRm) NSCLC, such as EGFR ex19del and L858R, resistance to these drugs is inevitable. BLU-945 is an investigational next-generation EGFR tyrosine kinase inhibitor (TKI) designed to suppress common activating and on-target resistance EGFR mutations, such as C797S and T790M. Preclinically it has shown activity as monotherapy in osimertinib-resistant patient-derived xenograft (PDX) models. In addition, BLU-945 has &gt; 450-fold selectivity for C797S and T790M mutants over wildtype, advantageous for combinations with complementary EGFR-targeting agents, such as osimertinib. These combinations have shown enhanced activity in PDX models. The SYMPHONY trial (BLU-945-1101; NCT04862780) is an international, open-label, first-in-human, phase 1/2 study designed to evaluate safety, tolerability, and antitumor activity of BLU-945 as monotherapy and in combination with osimertinib in patients with EGFRm NSCLC. Methods: Key eligibility criteria include adults with pathologically confirmed metastatic NSCLC with an activating EGFR mutation, Eastern Cooperative Oncology Group performance status 0–1, and previous treatment with ≥1 EGFR-targeted TKI. Patients with asymptomatic brain metastases who are on stable doses of corticosteroids are eligible. Tumors with additional known driver alterations, including EGFR exon 20 insertions and other kinase drivers, are excluded. Primary endpoints are maximum tolerated dose, recommended phase 2 dose (RP2D) and safety (phase 1); and overall response rate (ORR) by RECIST 1.1 (phase 2). Key secondary endpoints include ORR, duration of response (DOR), pharmacokinetics (PK), and pharmacodynamics (PD; phase 1); and DOR, progression-free survival, overall survival, CNS efficacy, PK, and safety (phase 2). Phase 1 dose escalation will be done using Bayesian optimal interval design; ̃85 patients will receive BLU-945 monotherapy and ̃18 will receive combination BLU-945 and osimertinib. In the phase 2 dose expansion, patients will receive BLU-945 at the RP2D of the monotherapy in 3 groups based on EGFR mutational profile: T790M and C797S (n≈37), T790M, but not C797S (n≈12), and C797S, but not T790M (n≈12). In a combination group, BLU-945 plus osimertinib will be administered at RP2D of the combination to n≈24 patients, ≥12 with both T790M and C797S mutations. Patients may receive treatment until disease progression or unacceptable toxicity. Recruitment has started and approximately 30 sites will be open for enrollment across North America, Europe, and Asia. Clinical trial information: NCT04862780.
A whole-food, plant-based (WFPB) dietary intervention to improve cancer-related and cardiometabolic outcomes in metastatic breast cancer patients.
Authors: Thomas Campbell, Erin Campbell, Eva Culakova, Michelle Christine Janelsins, Karen Michelle Mustian, Charles Stewart Kamen, Po-Ju Lin, Joseph John Guido, Luke Joseph Peppone
Journal: Journal of Clinical Oncology (2022)

e24116 Background: Obesity rates in the US have increased dramatically in recent years. Breast cancer treatment is associated with additional weight gain, and among patients with breast cancer, obesity and weight gain are associated with negative outcomes such as reduced progression-free and overall survival due to cardiometabolic co-morbidities. New evidence suggests that cardiometabolic comorbidities themselves can further accelerate breast cancer progression. We used a WFPB dietary intervention because it results in significant weight loss and larger improvements in cardiometabolic outcomes than a traditional, calorie-restricted omnivore diet. Methods: Patients with stage 4 breast cancer receiving treatment were randomized 2:1 into: 1) a WFPB dietary intervention (N = 19) or 2) usual care (N = 9) for 8 weeks with assessments at baseline, 4, and 8 weeks. Our WFPB diet consisted of education and an ad libitum whole-food, plant-based diet; 3 prepared meals a day were provided to WFPB subjects for the duration of the trial. The diet included fruits, vegetables, whole grains, legumes, nuts/seeds and excluded meat, dairy, and eggs. Outcomes include compliance, weight, cardiometabolic outcomes, and cancer progression markers. Effects of the WFPB on the outcomes were assessed by comparing marginal means by arm estimated at 8 weeks from the analysis of covariance model controlling for baseline. Results: Dietary compliance was high, with 95% of WFPB subjects consuming ≥80% of their calories from on plan foods. The WFPB group (mean baseline BMI = 31.6 kg/m 2 ), on average, lost 6.7% (p &lt; 0.01) of their total body weight. Adjusting for baseline weight, the WFPB group lost 8.9 lbs. more (p &lt; 0.01) and 5.8% more of their total body weight (p &lt; 0.01) than the control group. Conclusions: Our WFPB dietary intervention resulted in clinically meaningful and statistically significant improvements in weight and cardiometabolic outcomes, with a trend towards improving a clinically used cancer progression marker. Larger studies with longer interventions are needed to confirm these findings and investigate the sustainability of the benefits. Clinical trial information: NCT03045289. [Table: see text]
Integrated safety summary of single-agent mirvetuximab soravtansine in patients with folate receptor α (FRα)-positive recurrent ovarian cancer: Phase 1 and 3 clinical trials.
Authors: Kathleen N. Moore, Domenica Lorusso, Ana Oaknin, Amit M. Oza, Nicoletta Colombo, Toon Van Gorp, David M. O'Malley, Susana N. Banerjee, Conleth G. Murphy, Philipp Harter, Gottfried E. Konecny, Patricia Pautier, Michael W. Method, Jiuzhou Wang, Michael J. Birrer, Robert L. Coleman, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2022)

5574 Background: Available chemotherapies for platinum-resistant ovarian cancer (PROC) have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is a first-in-class antibody drug conjugate (ADC) comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent that has demonstrated significant anti-tumor activity in this difficult to treat population. The objective is to characterize the tolerability profile of MIRV in a pooled analysis of experience when administered as monotherapy in patients (pts) with FRα positive recurrent ovarian cancer. Methods: Retrospective pooled analysis included pts enrolled across three studies: phase 1 first-in-human, phase 3 FORWARD I, and phase 3 SORAYA. Analysis included pts with FRα positive recurrent ovarian cancer and those pts with low, medium, and high FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 25% of cells with PS2+ staining intensity). All pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. Results: 464 pts were included from 15 countries, with key characteristics: median age 63 yrs, 87% 1-3 prior therapies, 91% platinum free interval ≤6 months, 65% prior bevacizumab, and 25% prior PARPi. The most common treatment-related adverse events (TRAE) (all grade, grade 3+) included blurred vision (42%, 3%), nausea (40%, 2%), diarrhea (33%, 2%), fatigue (31%, 2%), keratopathy (26%, 3%), and dry eye (22%, 1%). TRAEs leading to a dose delay or reduction occurred in 33% and 21% of pts, respectively. Seven % discontinued due to a TRAE. Four pts ( &lt; 1%) discontinued MIRV due to an ocular event. Ninety % of pts with a grade 2+ blurred vision resolved to grade 0 or 1, 93% of pts with grade 2+ keratopathy resolved to grade 0 or 1. No corneal ulcers or perforation have been reported and no patient with a serious ocular event has been reported to have permanent sequelae. Conclusions: In a pooled analysis of 464 patients, MIRV monotherapy has a differentiated and predictable safety profile consisting primarily of low grade and reversible gastrointestinal and ocular events. These events were managed with supportive care and dose modifications if needed, with a low rate of treatment-related discontinuation. The safety profile of MIRV in recurrent ovarian cancer along with the anti-tumor activity in PROC (32.4% ORR Matulonis SGO 2022) support a favorable benefit/risk in this population. Clinical trial information: NCT01609556, NCT04296890, NCT02631876.
Comparison of simulated outcomes between stool- and blood-based colorectal cancer screening tests.
Authors: A. Fendrick, Vahab Vahdat, Jing Voon Chen, David A. Lieberman, Jordan J. Karlitz, Paul J. Limburg, A. Burak Ozbay, John B. Kisiel
Journal: Journal of Clinical Oncology (2022)

10529 Background: The Centers for Medicare &amp; Medicaid Services (CMS) recommends covering blood-based biomarker tests with proposed minimum performance thresholds for colorectal cancer (CRC) screening test every 3 years for average-risk, asymptomatic Medicare beneficiaries ages 50–85 years. A blood-based test is a non-invasive screening method to detect CRC but is limited by low sensitivity to detect adenomas. Using the CRC-AIM microsimulation model, predicted life-years gained (LYG) and CRC incidence and mortality reduction were compared between a blood-based test meeting the CMS minimum thresholds and stool-based screening tests (fecal immunochemical test [FIT], fecal occult blood test [FOBT], and multitarget stool DNA [mt-sDNA]). Methods: Outcomes of blood- and stool-based tests were simulated for average-risk individuals free of diagnosed CRC at age 40 and screened between ages 45–75 years per USPSTF recommendations. Per CMS proposed criteria, CRC sensitivity and specificity for a blood-based test were set at 74% and 90%, respectively, and adenoma sensitivity was set at 10%. Published adenoma and CRC sensitivity and specificity were used for each stool test. For the primary analysis, adherence was assumed to be 100%. For secondary analysis, adherence was set at 30–70%, in 10% increments. Outcomes were per 1000 individuals. Results: At 100% adherence, LYG was 229 for a blood test and ≥305 for stool tests, corresponding to at least 25% lower LYG for a blood test relative to all stool tests (Table). Absolute CRC incidence and mortality reductions were at least 19% and 18% lower, respectively, for a blood test vs all stool tests. Secondary analysis indicates that at identical adherence rates that are less than 100%, a blood test had lower LYG vs all stool tests (Table). When the adherence of any test was 50%–70%, a blood test resulted in at least 20% lower LYG vs any stool test, and absolute reductions in CRC incidence and mortality were at least 9% and 10% lower, respectively, vs any stool test. Conclusions: This model suggests that if blood-based CRC screening tests do not sufficiently detect advanced adenomas, clinical outcomes will be inferior to stool-based testing due to lack of cancer prevention. Further discovery efforts to identify blood-based markers associated with both invasive and preinvasive neoplasia are needed to address this deficiency. [Table: see text]
Does the 4R oncology model improve clinicians’ effectiveness in patient-facing planning of complex cancer care?
Authors: Julia R. Trosman, Swati Kulkarni, Rachel Podrazik Baer, Lawrence Eric Feldman, Mary Pasquinelli, Sheetal Mehta Kircher, Al Bowen Benson, William John Gradishar, Bruce Rapkin, Della F. Makower, Claudia Beth Perez, Stephanie Boecher, Arliene Ravelo Mangalindan, Elaine Yu, Christine B. Weldon
Journal: Journal of Clinical Oncology (2022)

1542 Background: The 4R Oncology model was proposed within the NCI ASCO Teams Project as an approach to facilitate patient-facing care planning, team-based delivery and patient self-management. 4R (Right Info/Care/Patient/Time) enables care teams and patients to manage complex care with a novel 4R Care Sequence plan. We previously reported that 4R significantly improved patient self-management, namely patients’ ability to organize and manage their care (Trosman JCO OP 2021). Here we report the impact of 4R on effectiveness of clinicians to plan and deliver complex multidisciplinary care. Methods: We surveyed clinicians (physicians and nurses) from 8 cancer centers (4 academic, 4 community) participating in a 4R adoption program. The survey was conducted Mar 2019 to Sep 2019 prior to 4R launch (Baseline cohort), and Nov 2021 to Jan 2022 post-4R launch (4R cohort). Baseline cohort included clinicians conducting care planning with patients. 4R cohort included clinicians who used 4R in care planning with new patients. The survey focused on clinicians’ self-reported effectiveness in planning and management of guideline-based care. Descriptive statistics and Fisher’s 2-sided test were used in analyses. Results: Baseline cohort’s response rate was 79% (66/83); 4R cohort’s response rate was 86% (62/72). 4R implementation was associated with significant improvement in all 5 metrics of effective care planning between the baseline and 4R cohorts (Table). Within the 4R cohort, 87% (54/62) clinicians found 4R Care Sequences useful or very useful for care planning and management. The majority, 79% (49/62), spent 10 minutes or less on average developing and administering 4R Care Sequence to a new patient, and 58% (36/62) reported decreased overall volume of post-visit inquiries about care plan from patients who received 4R. When asked about 4R delivery format, 65% (40/62) preferred paper, 23% (14/62) electronic delivery and 12% (8/62) had no preference. Conclusions: The 4R Oncology model is a promising approach to improving clinicians’ effectiveness in patient-facing care planning and reducing the workload associated with patient inquiries. An ongoing 4R research and implementation program continues efforts to identify optimal implementation methods and integrate 4R into clinical practice across the U.S. [Table: see text]